Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis

Abstract

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients’ age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes

“…There is no study illustrating the effect of specific Veillonella strain in PSC. The relative abundance of Veillonella genera were also increased in children and teenagers with PSC (Cortez et al, 2020). Intriguingly, it has been proved that the abundance of Veillonella decreased after effective treatment of UDCA (Kummen and Hov, 2019).…”

Editorial: The Microbiome in Hepatobiliary and Intestinal Disease

“…The various autoimmune liver diseases exhibit similar gut microbiome alterations: Stool samples of patients with autoimmune hepatitis are characterized by large quantities of Veillonella ( Elsherbiny et al, 2020 ; Liwinski et al, 2020 ; Lou et al, 2020 ; Wei et al, 2020 ), Streptococcus ( Elsherbiny et al, 2020 ; Liwinski et al, 2020 ; Wei et al, 2020 ), Haemophilus ( Elsherbiny et al, 2020 ; Lou et al, 2020 ), and Klebsiella ( Lou et al, 2020 ; Wei et al, 2020 ), and small quantities of Bifidobacterium ( Lin et al, 2015 ; Liwinski et al, 2020 ), Parabacteroides ( Elsherbiny et al, 2020 ; Lou et al, 2020 ; Wei et al, 2020 ), and Ruminococcaceae ( Lou et al, 2020 ; Wei et al, 2020 ). Primary biliary cholangitis is associated with an elevated abundance of Streptococcus ( Lv et al, 2016 ; Tang et al, 2018 ; Furukawa et al, 2020 ), Veillonella ( Lv et al, 2016 ; Abe et al, 2018 ; Tang et al, 2018 ), Klebsiella ( Lv et al, 2016 ; Tang et al, 2018 ), Haemophilus ( Lv et al, 2016 ; Tang et al, 2018 ), and Lactobacillus ( Tang et al, 2018 ; Furukawa et al, 2020 ), and diminished Ruminococcus /Ruminococcaceae ( Lv et al, 2016 ; Furukawa et al, 2020 ) and Faecalibacterium ( Tang et al, 2018 ; Furukawa et al, 2020 ), while primary sclerosing cholangitis is linked to enlarged proportions of Veillonella ( Bajer et al, 2017 ; Kummen et al, 2017 ; Rühlemann et al, 2019 ; Cortez et al, 2020 ; Lapidot et al, 2021 ), Streptococcus ( Sabino et al, 2016 ; Bajer et al, 2017 ; Rühlemann et al, 2019 ; Lapidot et al, 2021 ), and Enterococcus ( Sabino et al, 2016 ; Bajer et al, 2017 ), as well as depressed proportions of Coprococcus ( Bajer et al, 2017 …”

Overabundance of Veillonella parvula promotes intestinal inflammation by activating macrophages via LPS-TLR4 pathway

“…The composition and diversity of intestinal microbiome are associated with many diseases including HSCR and HAEC [ 5 – 9 ]. The host and the intestinal flora were found to be interactive [ 10 ].…”